Melatonin ameliorates TNFα-induced oral epithelial cell inflammation via Keap1-Nrf2 axis modulation.

BACKGROUND: Oral mucosal inflammatory diseases comprise a diverse array of conditions that affect the delicate tissues lining the oral cavity, posing a multifaceted challenge in clinical practice. Further studies are needed to elucidate the pathogenesis of these conditions. Melatonin has emerged as a promising antioxidant that scavenges free radicals and attenuates oxidative stress, a key contributor to inflammatory processes. METHODS: This study employed two oral epithelial cell lines, human oral epithelial cells (HOEC) and human oral keratinocytes (HOK), alongside a three-dimensional (3D) epithelial cell model, to investigate the effects of melatonin on oral epithelial inflammation. RESULTS: The findings revealed that TNFα significantly induced inflammation in oral epithelial cells, whereas melatonin inhibited TNFα-induced inflammation. Furthermore, melatonin's action in mitigating inflammation in oral epithelial cells was mediated via its receptor, MTNR1A. Mechanistically, melatonin suppressed inflammation in oral epithelial cells through the Keap1/Nrf2 signaling pathway. Additionally, melatonin attenuated TNFα-induced inflammation in the 3D oral epithelial cell model. CONCLUSION: These findings offer novel insights into the potential development of therapies for treating oral epithelial inflammation.